The overall objectives of this project will be to gain a basic understanding of the mechanism of hormone-mediated discharge in the pancreatic acinar cell, and to establish an experimental model for pancreatic cancer to aid in the study of etiology, diagnosis and treatment of this disease. This will be accomplished by characterizing the hormone-responsiveness and surface membrane components of a moderately-differentiated transplantable rat pancreatic acinar carcinoma (Reddy, J.K. and M. S Rao (1977) Science, 198: 78-80). Specific aims are to: (1) compare the discharge response of normal pancreatic acini to that of tumor cells regarding efficacy and potency of secretagogues, increases in cGMP, changes in intracellular calcium, and the role of calmodulin (also known as calcium-dependent regulatory protein or CDR); (2) compare surface properties in terms of number, affinity and distribution of peptide hormone receptors and antigenic or iodinatable components on the plasma membrane; and (3) adapt the pancreatic carcinoma to in vitro culture and study differentiation and morphogenesis. Normal acini and dissociated tumor cells will be prepared using purified collagenase. Secretion stimulated by caerulein, carbamylcholine, and other agents will be measured by release of amylase and pulse-labeled protein. Peptide hormone receptors will be studied using 125I or fluorescent derivatives. Antisera to tumor cells will be absorbed with normal tissue and used in immunoprecipitation of detergent-solubilized cell extracts coupled with cell iodination, gel electrophoresis and autoradiography. Characterization will be aided by correlation of results from all areas.